The characterization and transmissibility of chromosome aberrations induced in peripheral blood lymphocytes by in vitro alpha-particle radiation

Peripheral blood lymphocytes were irradiated in vitro with (213)Bi alpha particles at doses of 0, 10, 20, 50, 100, 200 and 500 mGy. Chromosome analysis was performed on 47-h cultures using single-color fluorescence in situ hybridization (FISH) to paint chromosomes 1, 3 and 5. The whole genome was analyzed for unstable aberrations to derive aberration frequencies and determine cell stability. The dose response for dicentrics was 33.60 +/- 0.47 x 10(-2) per Gy. A more detailed analysis revealed that the majority of aberrations scored as dicentrics were part of complex/multiple aberrations, with the proportion of cells containing complexes increasing with dose. Cells containing aberrations involving painted chromosomes (FISH aberrations) were further classified according to cell stability and complexity. The majority of cells with FISH aberrations were unstable. The proportion of aberrant FISH cells with complex/multiple aberrations ranged from 56% at 10 mGy to 89% at 500 mGy. A linear dose response for genomic frequencies of translocations in stable cells fitted the data from 0 to 200 mGy with a dose response of 7.90 +/- 0.98 x 10(-2) per Gy, thus indicating that they are likely to be observed in peripheral blood lymphocytes from individuals with past or chronic exposure to high-LET radiation. Comparisons with the dose response for low-LET radiation suggest an RBE of 13.6 for dicentrics in all cells and 3.2 for translocations in stable cells. Since stochastic effects of radiation are attributable to genetic changes in viable cells, translocations in stable cells may be a better measure when considering the comparative risks of different qualities of radiation.     

Variation in the frequencies of spontaneous and in vitro induced chromosome aberrations in human lymphocytes during natural and radiation-induced aging

The frequency of translocations detected by FISH in lymphocytes of control donors increases with age as a quadratic function. This process is faster in persons previously exposed to low doses of radiation. It means that translocation frequency can be used as a measure of biological age. Moreover, translocation frequency should be taken into account in biological reconstruction of absorbed doses. The frequencies of dicentrics detected by FIGH and FPG linearly increase with age in both groups, and this process occurs at equal rates during natural and radiation-induced aging. The age-dependent increase in the frequency of translocations exceeds the increase in dicentrics. The radiation sensitivity of lymphocytes estimated from the frequency of in vitro induced chromosomal aberrations tends to increase with age in the control group and decreases significantly in the group exposed to radiation; i.e., low-dose preexposure alters the pattern of the age dependence of radiation sensitivity in lymphocytes in vitro.     

Cesium-induced chromosome aberrations analyzed by fluorescence in situ hybridization: eight years follow up of the Goiânia radiation accident victims

The radiation accident in focus here occurred in a section of Goiânia (Brazil) where more than a hundred individuals were contaminated with ¹³⁷Cesium on September 1987. In order to estimate the absorbed radiation doses, initial frequencies of dicentrics and rings were determined in 129 victims [A.T. Ramalho, PhD Thesis, Subsidios a tecnica de dosimetria citogenetica gerados a partir da analise de resultados obtidos com o acidente radiologico de Goiânia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 1992]. We have followed some of these victims cytogenetically over the years seeking for parameters that could be used as basis for retrospective radiation dosimetry. Our data on translocation frequencies obtained by fluorescence in situ hybridization (FISH) could be directly compared to the baseline frequencies of dicentrics available for those same victims. Our results provided valuable information on how precise these estimates are. The frequencies of translocations observed years after the radiation exposure were two to three times lower than the initial dicentrics frequencies, the differences being larger at higher doses (> 1 Gy). The accuracy of such dose estimates might be increased by scoring sufficient amount of cells. However, factors such as the persistence of translocation carrying lymphocytes, translocation levels not proportional to chromosome size, and inter-individual variation reduce the precision of these estimates.     

Seventeen-year follow-up study on chromosomal aberrations in five victims accidentally exposed to several Gy of <Superscript>60</Superscript>Co γ-rays

On 25 June 1990, a radiation accident occurred in a ⁶⁰Co source radiation unit in Shanghai, due to violations in operation regulations. This accident resulted in the exposure of seven individuals to acute high-dose and dose-rate whole-body external irradiation. Conventional chromosomal aberration analysis, G-banding automatic karyotype analysis and/or fluorescent in situ hybridization (FISH) painting methods were used to analyze chromosomal aberrations in peripheral blood lymphocytes from five of the victims 24 h to 17 years after accidental exposure to 1.9–5.1 Gy of ⁶⁰Co γ-rays. The frequency of unstable chromosomal aberrations (dicentrics and rings) remained at constant levels 1 month after exposure. Three months after exposure, the frequency was reduced by 20–40% in three victims, while no reduction was seen in the other two victims. Twelve years after exposure, the number of dicentrics and rings decreased by more than 90%, and did not reveal a dose-dependent relationship. However, even at 12–17 years after exposure, stable chromosome aberrations, dominated by translocations, remained at a high level in a dose-dependent manner. The frequency of stable chromosomal aberrations detected by FISH showed a similar dose-dependent relationship as that detected by karyotype analysis of G-banding chromosomes. The G-banding analysis also suggested that the pattern of chromosome breakpoints is random. The FISH data showed a decreasing tendency with time for chromosome translocation frequency in the peripheral lymphocytes, and the rate of reduction varied among different individuals. It is likely that the higher dose the victim received, the lesser the translocation frequency decreased with time. The G-banding data also showed that the rate of reduction of translocations is different among individuals. From 5 to 17 years after accidental irradiation, a very small reduction (~10%) of translocation frequency was observed in victims C and D, while there was about a 35% reduction (the highest among the victims) for victim G who received the smallest dose (1.9 Gy). These observations can be used to validate the existence of chromosomal aberrations in peripheral blood lymphocytes as a biological dosimeter for radiation exposures.     

Possibilities and limitations of fluorescence in situ hybridization technique in retrospective detection of low dose radiation exposure in post-chernobyl human cohorts

Cytogenetic analysis using the fluorescence in situ hybridisation (FISH) technique was performed late time after the Chernobyl accident in groups of liquidators, evacuees from 30 km exclusive zone, residents of radioactively contaminated areas and control donors age-matched to exposed persons. Stable and unstable chromosome type exchanges were recorded using a hybrid conventional-PAINT nomenclature. The mean yield of stable chromosome exchanges in liquidators did not correlate with registered radiation doses but had a clear negative dependence on the duration of liquidators' staying in Chernobyl zone, that was in a good agreement with early data based on conventional dicentrics plus rings analysis. The overspontaneous excess for stable chromosome exchange level appeared to be higher in evacuees 16-40 years old than that of senior persons, whereas no age-dependent difference occurred for initially induced dicentrics plus rings yields in this cohort. The stable chromosome exchange yield, as well as combined yield of dicentrics plus rings and potentially unstable incomplete translocations in residents of radioactively contaminated areas showed a reasonable positive correlation with levels of 137Cs contamination. The observed yields of stable chromosome exchanges in all three exposed groups appeared to be somewhat lower than those of expected from unstable exchange-based doses which were referred to an in vitro dose response of stable exchanges outcome in human lymphocytes. Thus, FISH analysis can be successfully applied for qualitative cytogenetic indication of past and chronic radiation exposure to low doses but further refinement of FISH-based system for quantitative dose assessment is still required. Some practical approaches of solving this task are discussed.     

Analysis of translocations in stable cells and their implications in retrospective biological dosimetry

The aim of the present study was to evaluate the influence of the exclusion of cells with unstable aberrations in the elaboration of dose-effect curves for translocations and their implications in biological dosimetry of past exposures. To establish dose-effect curves, peripheral blood samples were irradiated with 60Co gamma rays at ten different doses and the yield of translocations analyzed by FISH was considered in all cells and in stable cells (those without dicentrics, acentrics or rings). To discriminate transmissible translocations, the dose- effect curve for total apparently simple translocations in stable cells was chosen as the reference. In stable cells, dose- effect curves for apparently simple translocations without pseudosimple and complex-derived one-way patterns, tAbtBa and total translocations were obtained. None of these curves differed from the reference curve. When all cells were considered, only the curve for total translocations was significantly different from the reference curve. From the results obtained it can be concluded that the use of dose-effect curves for apparently simple translocations in stable cells and in all cells will give similar dose estimates in retrospective biological dosimetry studies. However, the use of dose-effect curves for total translocations in all cells will lead to underestimations of the dose mainly at high doses.     

Cytogenetic evaluation of occupational exposure to external γ-rays and internal

Chromosome aberration analysis in astronauts has been used to provide direct, biologically motivated estimates of equivalent doses and risk associated to cosmic radiation exposure during space flight. However, the past studies concentrated on measurements of dicentrics and translocations, while chromosome intrachanges (inversions) have never been measured in astronauts’ samples. Recent data reported in the literature suggest that densely ionizing radiation can induce a large fraction of intrachanges, thus leading to the suspicion that interchanges grossly underestimate the cosmic radiation-induced cytogenetic damage in astronauts. We have analyzed peripheral blood lymphocytes from 11 astronauts involved in short- or long-term space flights in low-Earth orbit using high-resolution multicolor banding to assess the frequency of intrachromosomal exchanges in both pre- and post-flight samples. We did not detect any inversions in chromosome 5 from a total of 2800 cells in astronauts’ blood. In addition, no complex type exchanges were found in a total of 3590 astronauts’ lymphocytes analyzed by multifluor fluorescence in situ hybridisation. We conclude that, within the statistical power of this study, the analysis of interchanges for biological dosimetry in astronauts does not significantly underestimate the space radiation-induced cytogenetic damage, and complex-type exchanges or intrachanges have limited practical use for biodosimetry at very low doses.     

Space radiation does not induce a significant increase of intrachromosomal exchanges in astronauts’ lymphocytes

Chromosome aberration analysis in astronauts has been used to provide direct, biologically motivated estimates of equivalent doses and risk associated to cosmic radiation exposure during space flight. However, the past studies concentrated on measurements of dicentrics and translocations, while chromosome intrachanges (inversions) have never been measured in astronauts’ samples. Recent data reported in the literature suggest that densely ionizing radiation can induce a large fraction of intrachanges, thus leading to the suspicion that interchanges grossly underestimate the cosmic radiation-induced cytogenetic damage in astronauts. We have analyzed peripheral blood lymphocytes from 11 astronauts involved in short- or long-term space flights in low-Earth orbit using high-resolution multicolor banding to assess the frequency of intrachromosomal exchanges in both pre- and post-flight samples. We did not detect any inversions in chromosome 5 from a total of 2800 cells in astronauts’ blood. In addition, no complex type exchanges were found in a total of 3590 astronauts’ lymphocytes analyzed by multifluor fluorescence in situ hybridisation. We conclude that, within the statistical power of this study, the analysis of interchanges for biological dosimetry in astronauts does not significantly underestimate the space radiation-induced cytogenetic damage, and complex-type exchanges or intrachanges have limited practical use for biodosimetry at very low doses.     

The significance of cytogenetic investigation for the estimation of Chernobyl accident consequences

The results of the cytogenetic investigation of people, which were exposed to radiation in the result of the Chernobyl NPP accident, were presented. Also the possibilities of the application of cytogenetic findings for dose estimations and for the prediction of the radiation influence consequences were examined. During the period of time since 1986 till 2004 the cytogenetic investigations of 1724 liquidators participating in the liquidation works after the Chernobyl accident were carried out. The radiation dose estimated by the frequency of dicentrics in 1986 was about 0.16 Gy. The doses for liquidators were determined by the frequency of translocations (FISH method) during the period from 1992 till 1995. For liquidators who worked in Chernobyl only in 1986 the average dose of radiation was about 0.19 Gy and for liquidators who worked repeatedly during the period from 1986 till 1995 - 0.39 Gy. There was shown that during the whole period of investigation (1986-2004) the frequency of dicentrics in peripheral blood lymphocytes was significantly higher than the control level. The cytogenetic investigation of Bryansk region inhabitants which was carried out in 1992-1994 discovered heightened value in 5 times than the control one. Findings are of great importance for the prediction of ill effects of radiation and for the development of sensitive criterions for early exposure disturbances in state of health.     

Cytogenetic analysis of peripheral blood lymphocytes of occupational workers exposed to low levels of ionising radiation.

The incidence of chromosomal aberrations was analysed in peripheral blood lymphocytes of occupationally exposed people having cumulative doses of 500 mSv. The exposed individuals showed higher frequencies of dicentrics as well as acentrics than normal controls. Absorbed radiation dose was calculated by using in vitro dose response curve established for Cobalt-60 gamma rays. In the control constituting 17 healthy individuals, two dicentrics were detected among 3700 metaphases analysed. In the exposed group 27 dicentrics and one centric ring was detected among 8400 metaphases analysed. Due to small number of dicentrics scored in each individual, the dose estimate suffers from a large statistical uncertainty. The collective dose was found to be 1.89 Gy. This is in good agreement with the corrected physical doses, assuming a mean life of 10 years for the disappearance of lymphocytes. The physical doses accumulated during the last 10 years of occupation were also in good agreement with the biological dose estimate.     

Low-dose ionizing radiation and chromosome translocations: a review of the major considerations for human biological dosimetry

Chromosome translocations are a molecular signature of ionizing radiation exposure. Translocations persist significantly longer after exposure than other types of chromosome exchanges such as dicentrics. This persistence makes translocations the preferred aberration type for performing radiation dosimetry under conditions of protracted exposure or when exposure assessments are temporally delayed. Low doses of radiation are inherently difficult to quantify because the frequency of induced events is low and the background level of translocations among unexposed subjects can show considerable variability. Analyses of translocation frequencies can be confounded by several factors, including age of the subject, lifestyle choices such as cigarette smoking, the presence of clones of abnormal cells, and possibly genotypic variability among subjects. No significant effects of gender or race have been observed, but racial differences have not been completely ruled out. Translocation analyses may be complicated by the presence of different types of exchanges, i.e., reciprocal or non-reciprocal, and because translocations sometimes occur as a component of complex exchanges that include other forms of chromosome rearrangements. Rates of radiation exposure, ranging from acute to chronic, are known to influence the accumulation of translocations and may also affect their persistence. The influences on translocation frequencies of low-dose radiation hypersensitivity as well as the bystander effect and the adaptive response remain poorly characterized. Thus, quantifying the relationship between radiation dose and the frequency of translocations in any given subject requires attention to multiple issues. Part of the solution to understanding the in vivo dose-response relationship is to have accurate estimates of the baseline levels of translocations in healthy unexposed subjects, and some work in this area has been accomplished. Long-term cytogenetic follow-up of exposed subjects is needed to characterize translocation persistence, which is especially relevant for risk analyses. More work also needs to be done in the area of quantifying the role of known confounders. Characterizing the role of genotype will be especially important. Improvements in the ability to use translocation frequencies for low-dose biological dosimetry will require scoring very large numbers of cells per subject, which may be accomplished by developing a rapid automated image analysis system. This work would enhance our comprehension of the effects of low-dose radiation exposure and could lead to significant improvements in understanding the relationship between chromosome damage and human health.     

A cytogenetic follow-up study of the victims of a radiation accident in Goiania (Brazil)

A radiation accident involving a cesium-137 therapy source occurred in Goiania (Brazil) in September 1987, in which more than 50 individuals were exposed to moderate to high doses (0.2-7 Gy) of gamma-radiation. A cytogenetic technique (i.e., frequencies of dicentrics and rings in peripheral lymphocytes) was employed to estimate the absorbed radiation dose. The follow-up study extending over more than 1 year indicated a decline in the frequencies of dicentrics in the lymphocytes. Using chromosome-specific biotinylated library probes for chromosomes 1, 2, 8 and 19, we studied the frequencies of chromosomal translocations and deletions and the incidence of aneuploidy in the lymphocytes of exposed individuals. In some individuals there was a significant increase in the frequency of translocations and aneuploidy. In other experiments, in which the frequencies of HPRT mutations were determined in lymphocytes using the BrdU-labeling method, some individuals showed an increase (from about 2- to 50-fold) in mutant frequencies.     

Biological dosimetry in a group of radiologists by the analysis of dicentrics and translocations

The results of a cytogenetic study carried out in a group of nine radiologists are presented. Chromosome aberrations were detected by fluorescence plus Giemsa staining and fluorescence in situ hybridization. Dose estimates were obtained by extrapolating the yield of dicentrics and translocations to their respective dose-effect curves. In seven individuals, the 95% confidence limits of the doses estimated by dicentrics did not include 0 Gy. The 99 dicentrics observed in 17,626 cells gave a collective estimated dose of 115 mGy (95% confidence limits 73-171). For translocations, five individuals had estimated doses that were clearly higher than the total accumulated recorded dose. The 82 total apparently simple translocations observed in 9722 cells gave a collective estimated dose of 275 mGy (132-496). The mean genomic frequencies (x100 +/- SE) of complete and total apparently simple translocations observed in the group of radiologists (1.91 +/- 0.30 and 2.67 +/- 0.34, respectively) were significantly higher than those observed in a matched control group (0.53 +/- 0.10 and 0.87 +/- 0.13, P < 0.01 in both cases) and in another occupationally exposed matched group (0.79 +/- 0.12 and 1.14 +/-0.14, P < 0.03 and P < 0.01, respectively). The discrepancies observed between the physically recorded doses and the biologically estimated doses indicate that the radiologists did not always wear their dosimeters or that the dosimeters were not always in the radiation field.     

Genotoxic effects of radiotherapy and chemotherapy on the circulating lymphocytes of breast cancer patients. I. Chromosome aberrations induced in vivo

Unstable chromosome aberrations were scored in peripheral blood lymphocytes (PBL) serially collected from 21 breast cancer patients before and after radiotherapy (RT), chemotherapy (CT) and combined treatments. Local radiotherapy as treatment for mammary cancer induced unstable chromosome aberrations in peripheral blood lymphocytes. Only a fraction of these lymphocytes were exposed to irradiation during treatment and the chromosomal damage observed in PBL was equivalent to that induced by irradiation in vitro with 2 Gy at high dose rate, i.e., about 4% of the total dose delivered locally. Chemotherapy alone did not induce such anomalies. Apart from the observed interindividual variations in either the level or the fate of dicentrics with time, different features of chromosome damage were found when chemotherapy was given before or after local cobaltotherapy: secondary chemotherapy did not alter the frequency and the overdispersed distribution of dicentrics observed after first-line radiotherapy; in contrast, when CT was given before radiotherapy, a lower dicentric frequency was scored, the distribution of dicentrics was not always found to be overdispersed and there was a time-dependent decrease in dicentrics after in vivo exposure.     

The cytogenetic effects of low doses of accelerated charged particles in human blood lymphocytes in vitro

The aim of the investigation was the study of cytogenetic effects in human blood lymphocytes of low doses of ionizing radiation in vitro. The analysis of unstable chromosome aberrations in human lymphocytes after irradiation by the accelerated ions 12C with the energy 500 MeV/nucleon and LET 10.7 keV/microm was carried out. Blood samples were irradiated on Nuclotron of the High Energy Laboratory of the Joint Institute for Nuclear Research. The doses of irradiation were in the range from 0.05 up to 1.0 Gy. Was shown that the frequency of unstable chromosome aberrations depends from the dose of ionizing radiation and can be described by linear function. At the doses 0.25-0.50 Gy the dose-independent curve was obtained for dicentrics and centric rings. The frequencies of dicentrics and centric rings as markers of the radiation action were slightly different for different donors that could be explained by different radiosensitivity. Using the calibration curve obtained earlier for gamma-rays coefficients of relative biological efficiency of accelerated 12C with the energy 500 MeV/nucleon were defined: they varied from 1.0 at the doses (0.5-1.0 Gy) up to 3.2 at the lower doses (0.05-0.25 Gy).     

Current status of biodosimetry based on standard cytogenetic methods

Knowledge about dose levels in radiation protection is an important step for risk assessment. However, in most cases of real or suspected accidental exposures to ionizing radiation (IR), physical dosimetry cannot be performed for retrospective estimates. In such situations, biological dosimetry has been proposed as an alternative for investigation. Briefly, biodosimetry can be defined as individual dose evaluation based on biological endpoints induced by IR (so-called biomarkers). The relationship between biological endpoints and absorbed dose is not always straightforward: nausea, vomiting and diarrhoea, for example, are the most well-known biological effects of individual irradiation, but a precise correlation between those symptoms and absorbed dose is hardly achieved. The scoring of unstable chromosomal-type aberrations (such as dicentrics and rings) and micronuclei in mitogen-stimulated peripheral blood, up till today, has been the most extensively biodosimetry assay employed for such purposes. Dicentric assay is the gold standard in biodosimetry, since its presence is generally considered to be specific to radiation exposure; scoring of micronuclei (a kind of by-product of chromosomal damages) is easier and faster than that of dicentrics for dose assessment. In this context, the aim of this work is to present an overview on biodosimetry based on standard cytogenetic methods, highlighting its advantages and limitations as tool in monitoring of radiation workers’ doses or investigation into accidental exposures. Recent advances and perspectives are also briefly presented.     

Retrospective dose estimation in remote period after exposure using different biological methods

Investigation of application of chromosome aberrations of lymphocytes in peripheral blood for biological dosimetry purposes in remote (up to 40 years) period after acute exposure to doses of 1 Gy and more was carried out. The comparative analysis of frequency of unstable and stable (using FISH and G-banding methods) aberrations was performed for 24 subjects accidentally exposed to radiation on nuclear submarines during 1961-1985. Statistically significant increasing of frequency of dicentrics and centric rings was determined in the exposed subjects in remote period after exposure to compare with controls. Their sum frequency in the exposed group varied depending on ARS heaviness from 0.1 to 1.0 aberrations per 100 cells. In control group it was from 0 to 0.2 correspondingly. Translocation frequency (complete + incomplete) fixed by FISH method (2, 4, and 12 chromosomes) varied within the limits of 0.2-16.0 for exposed subjects and 0.3-1.26 translocations per genome per 100 cells for controls. Some examined persons (5 subjects) exposed to accident in 1985 had results of analysis of unstable chromosome aberration in acute period after exposure that allow to estimate obtained doses by dicentrics frequency which having good correlation with ARS heaviness. Individual dosed using traslocation frequency were defined retrospectively in 11 from 21 exposed persons. They correlate with calculated physics doses and doses estimated by haematolotical parameters in acute period and also doses obtained by ESR spectroscopy of tooth enamel in remote period.     

The low dose and low dose rate cytogenetic effects induced by gamma-radiation in human blood lymphocytes in vitro. II. the results of cytogenetic study

The yield of chromosome aberrations induced by gamma-radiation of 60Co in human blood lymphocytes in vitro at low doses (30 divided by 600 mGy) and low dose rates (0.70, 5.05, 59.2 mGy/min) was investigated. It was found that the observed level of chromosomal aberrations induced by gamma-irradiation was unaffected by the value of the dose rate when using constant dose rate and obtaining different doses by altering the exposure time. However, a relatively enhanced level of chromatid aberrations was found at 5.05 and 59.2 mGy/min dose rates in the dose range less than 250 mGy. We have found that the observed level of the sum of chromosomal aberrations induced by gamma-irradiation at doses less than 250 mGy and a dose rate of 59.2 mGy/min was essentially larger compared with the level extrapolated from high doses (above 300 mGy) using a linear-quadratic dose curve. This complied with our previous finding in 1976, 1977 when the enhanced level of dicentrics was only found at a high dose rate approximately 500 mGy/min. Such a non-linear cytogenetic effect does not manifest itself statistically significantly at dose rates of 0.70 and 5.05 mGy/min for the sum of chromosomal aberrations and does not manifest itself at all for dicentrics at all the examined dose rates.     

Ratio of acentrics to dicentrics in human lymphocytes exposed to X rays and misonidazole

A 0.8 mM concentration of misonidazole was added to human blood samples before exposure to graded X-ray single doses, in order to investigate the dependence of the frequency ratio of acentrics to dicentrics, produced in lymphocytes, on treatment with radiation, the substance and the combination of the 2 agents. The results confirm the findings of a previous experiment carried out using sodium iothalamate, showing that this ratio is markedly influenced by the relative action of the physical and the chemical agents, especially at low radiation doses, because of the enhancement of the frequency of acentrics, and not of dicentrics, caused by the presence of the drug compared to the spontaneous level.     

The cellular lethality of radiation-induced chromosome translocations in human lymphocytes

Recent evidence has shown that translocation frequencies decline over time. This phenomenon might be explained by the co-occurrence of translocations in cells that also contain dicentrics, in which case translocations would be eliminated as a by-product of selection against dicentrics. Alternatively, a fraction of translocations may themselves be lethal. Here we describe our initial approaches to develop mathematical models to test whether the decline in translocation frequencies results from the first, the second, or a combination of these two possibilities. The models assumed that all chromosome exchanges were simple, i.e., were comprised of dicentrics as well as one-way and two-way translocations. Complex aberrations (three or more breaks in two or more chromosomes) were not modeled, nor were fragments or intrachromosomal exchanges (rings, inversions). We tested the models using Monte Carlo simulations, and then we fitted the models to data describing chromosome aberration frequencies induced by a single acute in vitro exposure to (137)Cs gamma rays in human peripheral blood lymphocytes from two donors. Chromosome painting was used to enumerate translocations and dicentrics from 2 to 7 days after exposure. Our results indicate that in donor no. 2, the decline in translocation frequencies occurs as a by-product of selection against dicentrics. However, in donor no. 1, whose cells appeared more radiosensitive than cells from donor no. 2, up to 40% of the one-way translocations may themselves be lethal at high doses, although calculations indicate that two-way translocations do not cause lymphocyte mortality. Individual variation in the probability that translocations are lethal to cells appears to be important, and one-way translocations appear to be lethal more often than two-way translocations. Within the limits of these models, these findings indicate that both postulated mechanisms, i.e. inherent lethality and selection against dicentrics in the same cells, contribute to the loss of both one-way and two-way translocations.